Multiple myeloma is a neoplastic disease which was thought to arise from a single plasma cell. Its etiology is unknown. Recent advances in chromosomal analysis have established the presence of a consistent abnormality (a 14q plus translocation) in many patients with malignant disease of the lymphoid system. This abnormality, along with a multitude of others, has been described in myeloma. Although myeloma is thought to be a disease of the end-stage cell of B-cell differentiation, the possibility exists that the neoplastic event occurs in a plasma cell precursor or a cell regulating B-cell function. We have devised techniques of separating plasma cells, and B and T lymphocytes from bone marrows as well as the peripheral blood in patients with multiple myeloma. We will isolate these individual cell populations from patients with myeloma and subject each of them to chromosomal analysis to establish the cell or origin of the neoplastic crest. We have found one patient whose cells, established in tissue culture, have chromosome markers in both B lymphocytes and plasma cells.